Corticosteroid therapy has been associated with bone toxicities (e.g. osteonecrosis) and Cushing?s syndrome in HIV-infected patients; this may be due ?in part- to a pharmacokinetic drug interaction between HIV protease inhibitors and corticosteroids. The purpose of this study was to characterize the influence of low-dose ritonavir on prednisolone pharmacokinetics in healthy subjects. Ten HIV seronegative volunteers were given single oral doses of prednisone 20 mg before (baseline), and after receiving ritonavir 200 mg twice daily for 4, and 14 days. After each prednisone dose serial blood samples were collected and prednisolone concentrations determined; pharmacokinetic parameter values were compared among the groups. Geometric mean ratios (GMRs, 90% CI) of prednisolone area under the plasma concentration vs. time curve (AUC0-Y) after 4, and 14 days of ritonavir vs. baseline were 1.41 (1.08-1.74) and 1.30 (1.09-1.49), respectively (P = .002 and .004, respectively). GMRs of prednisolone apparent oral clearance (Cl/F) were 0.71 (0.57-0.93) and 0.77 (0.67-0.92) after 4, and 14 days of ritonavir vs. baseline, respectively (P = .0004 and .0003, respectively). Ritonavir significantly increased the systemic exposure of prednisolone in healthy subjects. Results from this investigation suggest that corticosteroid exposure is likely elevated in HIV-infected patients receiving protease inhibitors. A secondary component of this study is to characterize the influence of antiretroviral medications that are CYP3A4 inhibitors (lopinavir + ritonavir) and inducers (nevirapine or efavirenz) on prednisolone pharmacokinetics in HIV+ individuals receiving a single dose of prednisone. A third (control) group, comprised of subjects not taking any CYP3A4-modulating agents will also be included in the investigation. Ten subjects per group will participate. Currently two subjects have been enrolled to date; data are not yet available on these individuals.